Abstract
In patients with triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs) are associated with improved survival. Lehmann et al. identified 4 molecular subtypes of TNBC [basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor (LAR)], and an immunomodulatory (IM) gene expression signature indicates the presence of TILs and modifies these subtypes. The association between TNBC subtype and TILs is not known. Also, the association between inflammatory breast cancer (IBC) and the presence of TILs is not known. Therefore, we studied the IM subtype distribution among different TNBC subtypes. We retrospectively analyzed patients with TNBC from the World IBC Consortium dataset. The molecular subtype and the IM signature [positive (IM+) or negative (IM-)] were analyzed. Fisher’s exact test was used to analyze the distribution of positivity for the IM signature according to the TNBC molecular subtype and IBC status. There were 88 patients with TNBC in the dataset, and among them 39 patients (44%) had IBC and 49 (56%) had non-IBC. The frequency of IM+ cases differed by TNBC subtype (p = 0.001). The frequency of IM+ cases by subtype was as follows: BL1, 48% (14/29); BL2, 30% (3/10); LAR, 18% (3/17); and M, 0% (0/21) (in 11 patients, the subtype could not be determined). The frequency of IM+ cases did not differ between patients with IBC and non-IBC (23% and 33%, respectively; p = 0.35). In conclusion, the IM signature representing the underlying molecular correlate of TILs in the tumor may differ by TNBC subtype but not by IBC status.
Highlights
Triple-negative breast cancer (TNBC) accounts for 10% to 20% of breast cancers
We previously reported that the TNBC subtype is a predictor of pathological complete response (pCR) after neoadjuvant chemotherapy [9]: the BL1 subtype was associated with the highest pCR rate (52%), and the BL2 and luminal androgen receptor (LAR) subtypes had the lowest pCR rates (0% and 10%, respectively)
We previously reported that the TNBC molecular subtypes are expressed in both inflammatory and non-inflammatory TNBC and that we found no unique inflammatory breast cancer (IBC)-specific TNBC subtypes by mRNA gene expression profiling [13]
Summary
TNBC is an aggressive tumor, and patients with TNBC have a higher risk of both local and distant recurrence compared to patients with other types of breast cancer [1]. Patients with TNBC have higher rates of pathological complete response (pCR) following neoadjuvant chemotherapy than patients with other types of breast cancer, but TNBC patients without a pCR have a markedly worse prognosis than TNBC patients with a pCR [2]. Several studies have shown that in patients with TNBC, there is a linear relationship between the number of tumor-infiltrating lymphocytes (TILs), mononuclear immune cells that infiltrate tumor, and recurrence-free survival [3,4,5]. It has been reported that in patients with breast cancer, the presence of TILs is associated with increased rates of pCR following neoadjuvant chemotherapy [6, 7].
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